The long term goal of this project is to improve our understanding of the complex biology of normal human respiratory epithelial (RE) cells by using an in vitro model to study the growth and differentiation of these cells. The clinical potential of the development of a successful in vitro model of RE cells would be three fold. First, such a model would allow further dissection of both normal and pathologic processes related to the upper aerodigestive tract. Second, the ability to culture and grow differentiated RE cells may allow these cells to be used to effect physiologic repair and reepithelialization in vivo of diseased or damaged structures in the upper aerodigestive tract, such as trachea, paranasal sinuses, larynx, and nasal vault. Third, maintaining a source of normal RE cells in vitro will allow analysis of the effects of various irritants, as well as pharmacologic agents on the function and structure of these cells. Using cellular, biochemical, immunologic and recombinant DNA techniques, our experimental approach is to examine potential mechanisms controlling the growth and differentiation of RE cells in vitro. the specific aims of this proposal are: (1) to determine the biological and biochemical requirements for the sustained growth and differentiation of NRE in tissue culture, and to determine if synthetic bioresorbable substrates can be used to support or promote the proliferation and/or differentiation of RE in vitro; (2) to determine the pattern of expression in noncultured RE cells, and in differentiated and undifferentiated cultured RE cells of important biomolecules including protooncogenes, growth factors, growth factor receptors, and integrins; (3) to determine the effects of introducing known oncogenes, growth factor genes, and growth factor receptor genes on the proliferation and differentiation of NRE grown in vitro. The complete or partial success of these aims will lead to a better understanding of the requirements for the survival, growth, extended proliferation, and differentiation of human RE cells in vitro, and, eventually, allow the development of these cells as potential grafts in areas within the upper aerodigestive tract injured due to ablative surgery and/or congenital defects.